P535: UPDATES FROM ITALIAN MULTICENTER REAL-LIFE EXPERIENCE ON CPX-351 THERAPY IN YOUNG PATIENTS (&lt;60 YEARS OLD).
Authors: B. Garibaldi, M. Franciosa, F. Pilo, D. Menotti, V. Cardinali, L. Brunetti, E. A. Martino, E. Vigna, I. Tanasi, A. Duminuco, C. Maugeri, M. S. Parisi, P. F. Fiumara, E. Mauro, M. Gentile, M. P. Martelli, D. Capelli, C. Romani, S. Galimberti, G. A. Palumbo, F. Di Raimondo, C. Vetro
Journal: HemaSphere (2022)

Background: CPX-351 has been indicated as a valid treatment approach in acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) and therapy-related AML (t-AML). Data on young patients are limited. Aims: Explore CPX-351 efficacy in younger patients (pts) (<60 years old) in real-life. Methods: Since September 2019 we treated 32 pts from 7 Italian centres with CPX-351. Median age was 55 (range 32-59) and ECOG range 0-2. Our cohort consisted in 6 pts with t-AML and 26 pts with MRC-AML (10 morphologic, 11 secondary to MDS, 3 secondary to MDS/MPN, 6 with MRC cytogenetics features including 2 secondary to MDS and 2 morphologic AML-MRC). 2 pts (both with AML-MRC) harboured FLT3-ITD and 1 patient FLT3-TKD, 4 pts IDH1 and 3 pts TP53 mutations. NPM1 was negative in all pts. 10 pts had complex karyotype (CK) and 5 pts received prior treatment with hypomethylating agents for MDS. Results: All pts underwent induction therapy with intravenous administration of CPX-351 at day 1, 3 and 5 except 1 patient who received two doses due to pneumonia. 2 pts (6%) died during induction. Most frequent complication was febrile neutropenia (46%). At disease re-evaluation, we obtained 16 (50%) Complete Remission (CR), 5 (16%) CR with incomplete hematological recovery (CRi), 1 (3%) Morphological Leukemia Free State (MLFS), 4 (12,5%) Partial Remission (after reinduction converted to 2 CR, 1 CRi, while 1 patient was refractory) and 4 (12,5%) refractory pts who switched to salvage therapies except for one who died due to disease progression. Overall response rate (ORR) was 68% after induction and 78% after reinduction. All 25 responding pts underwent consolidation, except one that proceeded directly to allogenic stem cell transplantation (HSCT). 16 out 25 responding pts (64%) underwent HSCT. CR rate in patient with CK was 60%. At induction, median days of severe neutropenia (defined as neutrophils ≤ 500/uL) and thrombocytopenia (defined as platelets ​​≤20.000/uL) were respectively 26 and 22. Regarding subgroup analysis by driving mutations, the 4 IDH1 pts obtained a CR and 3 of them received HSCT. 2 out of 3 TP53 pts were refractory and the other one obtained a CR followed by HSCT. About the 2 FLT3-ITD pts, one died during induction and the other one obtained CR after reinduction and then underwent HSCT. After a median follow-up of 19 months (mo), 6 pts out of the 25 who reached CR/CRi (24%) relapsed and 20 out of 32 (63%) pts are alive. Median relapse-free survival (RFS) for responding pts was not reached. RFS was inferior for t-AML compared to AML-MRC (7 mo vs not reached median, p=0.032). RFS was negatively influenced by CK (median RFS 7 mo for CK vs not reached if no CK, p=0.009) and performance status (PS) (median RFS not reached for PS 0 vs 15 months for PS 1 vs 7 mo for PS 2, p=0.017). Median overall survival (OS) was 20 mo. Pts responding to induction did not reach median OS, while refractory pts had a median OS of 9 months. Noteworthy, OS was not influenced by cytogenetic risk, subtype of AML (if MRC or t-AML) or mutational status. Pts undergoing HSCT at first CR, did not reach median OS, while not transplanted pts had a median OS of 17 mo. COX multivariate analysis showed that reaching CR was the only significative parameter for OS (HR 8, 95% CI 1.18-54). Summary/Conclusion: CPX-351 is active in young pts with t-AML and AML-MRC with an ORR higher than that reported in the pivotal study (78% vs 47%) and high rate of bridge to transplant at first remission (56%) also considering the different age range. CK and PS 1-2 negatively impacted RFS. OS was influenced by response to induction and HSCT.